Locally acting ACE-083 increases muscle volume in healthy volunteers

Chad E Glasser, Michael R Gartner, Dawn Wilson, Barry Miller, Matthew L Sherman, Kenneth M Attie, Chad E Glasser, Michael R Gartner, Dawn Wilson, Barry Miller, Matthew L Sherman, Kenneth M Attie

Abstract

Introduction: ACE-083 is a locally acting follistatin-based therapeutic that binds myostatin and other muscle regulators and has been shown to increase muscle mass and force in neuromuscular disease mouse models. This first-in-human study examined these effects.

Methods: In this phase 1, randomized, double-blind, placebo-controlled, dose-ranging study in healthy postmenopausal women, ACE-083 (50-200 mg) or placebo was administered unilaterally into rectus femoris (RF) or tibialis anterior (TA) muscles as 1 or 2 doses 3 weeks apart.

Results: Fifty-eight postmenopausal women were enrolled, 42 ACE-083 and 16 placebo. No serious adverse events (AE), dose-limiting toxicities, or discontinuations resulting from AEs occurred. Maximum (mean ± SD) increases in RF and TA muscle volume were 14.5% ± 4.5% and 8.9% ± 4.7%, respectively. No significant changes in mean muscle strength were observed.

Discussion: ACE-083 was well tolerated and resulted in significant targeted muscle growth. ACE-083 may have the potential to increase muscle mass in a wide range of neuromuscular disorders. Muscle Nerve 57: 921-926, 2018.

Trial registration: ClinicalTrials.gov NCT02257489.

Keywords: ACE-083; muscle volume; muscular dystrophy; myostatin; neuromuscular disease.

© 2018 The Authors Muscle & Nerve Published by Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
Mean ± SEM percentage change from baseline in muscle volume according to MRI in the right (ACE‐083‐injected) muscle at 3 weeks and 8 weeks after the last dose. (A) Rectus femoris. (B) Tibialis anterior. *P < 0.05, **P < 0.001, Dunnett's test vs. placebo.
Figure 2
Figure 2
Correlation between right (ACE‐083‐injected) muscle volume increase at 3 weeks after last dose and ACE‐083 dosage per gram muscle (according to MRI for each participant). (A) Rectus femoris cohorts 4 and 5. (B) Tibialis anterior cohorts 6 and 7.

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